The overall objective of the proposed study is directed toward elucidation of the origin of human pandemic influenza viruses. Studies on the persistence of influenza virus genetic information in infected animals using marker rescue techniques has shown that antigenic hybrid viruses cannot be isolated after the initial replication period. The gene product(s) responsible for the intrinsic virulence of influenza viruses is being studied with temperature sensitive (ts) mutants and RNA gel analysis of A/turkey/Ontario/7732/66 (Hav5 Nav6) influenza virus. Ten ts mutants have been divided into 5 complementation groups and analysis of the RNAs of recombinant influenza viruses is permitting us to determine the origin of RNA segments and to correlate them with biological functions. Our studies on the importance of the "common" and "specific" determinants on the hemagglutinin subunits of influenza virus has shown that high doses of subunit vaccines in man will produce antibodies to the specific determinants on the hemagglutinin subunits. A new group of influenza viruses was characterized that have a hitherto unidentified neuraminidase and was designated Nav6. A new hemagglutinin group possessing Hav9 was also characterized. BIBLIOGRAPHIC REFERENCES: Webster, R.G., Kasel, J.A., Couch, R.B. and Laver, W.G. Influenza virus subunit vaccines. II. Immunogenicity and original antigenic sin in man. J. Inf. Dis. 134:48-58, 1976. Green, Alexander A., Pratt, Charles, Webster, Robert G., and Smith, Kirby: Immunotherapy of osteosarcoma patients with virus-modified tumor cells. Ann. N.Y. Acad. Sci. Vol. 277, 396-411, 1976.